Prostate cancer is a cancer which manifests in men most frequently in Europe and United States. Also in Japan, with westernization of dietary habits and aging of population, the number of patients suffering from prostate cancer is increasing drastically. Methods used widely for the treatment of prostate cancer are surgical therapy including prostatectomy, chemotherapy with an anticancer agent, and radiation therapy. Surgical therapy is the first-line treatment, but when cancer is diagnosed as being in an advanced stage or when surgery cannot be selected because it is a recurrent cancer after surgery, a therapeutic method other than surgery is selected.
In general, proliferation of prostate cancer is stimulated by androgen. Androgen is a steroid hormone having functions such as sex differentiation into male, function maintenance of reproductive organs, secondary sexual development, spermatogenesis, and promotion of anabolic action in skeletal muscles and the like. Two androgens (testosterone and dihydrotestosterone (DHT) are mainly involved in masculinization of humans. Testosterone is, after synthesis in testicular interstitial cells, transported to target cells such as prostate cells via the blood stream. In the cells, testosterone is converted into DHT by 5-α-hydrogenase and the resulting DHT binds to an androgen receptor (AR) in the cytoplasm. AR bound to DHT becomes an active type, is transported into the nucleus, and binds to an androgen responsive sequence on the target gene to function as a transcription factor activating expression of the target gene.
As therapeutic methods of prostate cancer other than surgical treatment, hormone therapy for inhibiting production and function of androgen is often employed and in most cases, it produces considerably good effects. Within several years after this hormone therapy, however, androgen-independent prostate cancer sometimes occurs. It therefore becomes an important object to control androgen-independent cancer.
Detailed molecular mechanism how androgen-dependent cancer progresses to androgen-independent cancer has not yet been elucidated, but involvement of AR in it has been suggested. More specifically, it has been suggested that in androgen independent cancer, AR which has undergone mutation or amplification shows sensitivity to ultra-low-concentration androgen or another steroid hormone (refer to, for example, Non-patent Documents 1 to 3). A method of treating prostate cancer by inhibiting binding of AR to ligand or inhibiting expression or function of AR by RNAi (RNA interference) method has been studied (refer to, for example, Non-patent Documents 4 to 6).
There is however a limitation in the method of inhibiting the function or expression of AR particularly for the treatment of prostate cancer which has recurred and a clinically sufficient method has not yet been developed.